After becoming assistant to Andrew Sellards, he started working on yellow fever. In 1926 they disproved Hideyo Noguchi's hypothesis that yellow fever was caused by the bacterium Leptospira icteroides. In 1928, the year after the disease was identified conclusively as a virus, they showed that the African and South American viruses are immunologically identical. (This followed Adrian Stokes' inducing yellow fever in Rhesus monkeys from India). In the course of this research, Theiler contracted yellow fever but survived and developed immunity.

In 1930 Theiler moved to the Rockefeller Institute in New York, where he later became director of the Virus Laboratory. He was professor of epidemiology and public health at Yale University from 1964 to 1967.

Work on yellow fever

After passing the yellow fever virus through laboratory mice, Theiler found that the weakened virus conferred immunity on Rhesus monkeys.[1] The stage was set for Theiler to develop a vaccine against the disease. Theiler first devised a test for the efficacy of experimental vaccines. In his test, sera from vaccinated human subjects was injected into mice to see if it protected the mice against Yellow Fever virus. This “mouse protection test,” was used with variations as a measure of immunity until after World War II.[1] Subculturing the particularly virulent Asibi strain from West Africa in chicken embryos, a technique pioneered by Ernest Goodpasture, the Rockefeller team sought to obtain an attenuated strain of the virus that would not kill mice when injected into their brains. It took until 1937, and more than one hundred subcultures in chicken embryos, for Theiler and his colleague Hugh Smith to obtain an attenuated strain, which they named "17D". Animal tests showed the attenuated 17D mutant was safe and immunizing. Theiler's team rapidly completed the development of a 17D vaccine, and the Rockefeller Foundation began human trials in South America. Between 1940 and 1947, the Rockefeller Foundation produced more than 28 million doses of the vaccine and finally ended yellow fever as a major disease.

Theiler's Murine Encephalomyelitis Virus (TMEV)

In 1937, Max Theiler discovered a filterable agent that was a known cause for paralysis in mice. He found the virus was not transmittable to Rhesus monkeys, and that only some mice developed symptoms.[2] The virus is now referred to as Theiler's murine encephalomyelitis virus. The virus has been well characterized, and now serves as a standard model for studying multiple sclerosis.